Low back pain is a leading cause of disability and lost productivity. Up to 90% of adults experience back pain at some time during their lives. Among frequency of physician visits, back pain is second only to upper respiratory infections. In the United States, this malady disables 5.2 million people, and the economic impact has been reported to be as high as $100 billion each year. Though the sources of low back pain are varied, in most cases the intervertebral disc is thought to play a central role.
The intervertebral disc absorbs most of the compressive load of the spine, but the facet joints of the vertebral bodies share approximately 16%. The disc consists of three distinct parts: the nucleus pulposus, the annular layers and the cartilaginous endplates. The disc maintains its structural properties largely through its ability to attract and retain water. A normal disc contains 80% water in the nucleus pulposus. The nucleus pulposus within a normal disc is rich in water absorbing sulfated glycosaminoglycans (chondroitin and keratan sulfate), creating swelling pressure to provide tensile stress within the collagen fibers of the annulus. The swelling pressure produced by high water content is crucial to supporting the annular layers and sustaining compressive loads.
In adults, the intervertebral disc is avascular. Survival of the disc cells depends on diffusion of nutrients from external blood vessels and capillaries through the cartilage of the endplates. Diffusion of nutrients also permeates from peripheral blood vessels adjacent to the outer annulus, but these nutrients can only permeate up to 1 cm into the annular layers of the disc. An adult disc can be as large as 5 cm in diameter; hence diffusion through the cranial and caudal endplates is crucial for maintaining the health of the nucleus pulposus and inner annular layers of the disc.
Calcium pyrophosphate and hydroxyapatite are commonly found in the endplate and nucleus pulposus. Beginning as young as 18 years of age, calcified layers begin to accumulate in the cartilaginous endplate. The blood vessels and capillaries at the bone-cartilage interface are gradually occluded by the build-up of the calcified layers which form into bone. Bone formation at the endplate increases with age.
When the endplate is obliterated by bone, diffusion of nutrients through the calcified endplate is greatly limited. In addition to hindering the diffusion of nutrients, calcified endplates further limit the permeation of oxygen into the disc.
The supply of sulfate into the nucleus pulposus for biosynthesizing sulfated glycosaminoglycans is also restricted by the calcified endplates. As a result, the sulfated glycosaminoglycan concentration decreases, leading to lower water content and swelling pressure within the nucleus pulposus. During normal daily compressive loading on the spine, the reduced pressure within the nucleus pulposus can no longer sustain most of the compressive load. The load is then transferred from the flattened disc to strain the facet joints, causing wear and pain.
The shear stresses on the disc are the highest at the posterolateral sides, adjacent to the neuroforamen. The nerve is confined within the neuroforamen between the disc and the facet joint. Hence, the nerve at the neuroforamen is vulnerable to impingement by the bulging disc or bone spurs.
When oxygen concentration in the disc is low, production of lactic acid dramatically increases. The pH within the disc falls as lactic acid concentration increases. Lactic acid diffuses through micro-tears of the annulus, irritating the richly innervated posterior longitudinal ligament, facet joint and/or nerve root. Studies indicate that lumbar pain correlates well with high lactate levels and low pH. The mean pH of symptomatic discs was significantly lower than the mean pH of normal discs. Acid concentration can be three times higher in symptomatic discs than normal discs. In symptomatic discs with pH 6.65, the acid concentration within the disc is 5.6 times the plasma level. In some preoperative symptomatic discs, nerve roots were found to be surrounded by dense fibrous scars with remarkably low pH 5.7-6.30. The acid concentration within these discs was 50 times the plasma level.
Approximately 85% of patients with low back pain cannot be given a precise pathoanatomical diagnosis. This type of pain is generally classified under “non-specific pain.” Back pain and sciatica can be recapitulated by maneuvers that do not affect the nerve root, such as intradiscal saline injection, discography, and compression of the posterior longitudinal ligaments. It is possible that some of the non-specific pain is caused by lactic acid irritation secreted from the disc. Injection into the disc can flush out the lactic acid. Maneuvering and compression can also drive out the irritating acid and produce non-specific pain. Currently, no intervention other than discectomy can halt the production of lactic acid.
In the presence of oxygen, metabolism of each glucose molecule produces 36 adenosine triphosphates, ATP, through glycolysis, citric acid cycle and the electron transport chain. ATP is a high-energy compound essential for driving biosynthesis of water-retaining proteoglycans. Under anaerobic conditions, the metabolism of each glucose molecule produces only 2 ATP and two lactic acids. Hence, production of high-energy compound ATP is low under anaerobic conditions, while production of lactic acid is high within the degenerated disc.
The nucleus pulposus is thought to function as “the air in a tire” to pressurize the disc. To support the load, the pressure effectively distributes the forces evenly along the circumference of the inner annulus and keeps the lamellae bulging outward. The process of disc degeneration begins with calcification of the endplates, which hinders diffusion of sulfate and oxygen into the nucleus pulposus. As a result, production of the water absorbing sulfated glycosaminoglycans is significantly reduced, and the water content within the nucleus decreases. The inner annular lamellae begin to sag inward, and the tension on collagen fibers within the annulus is lost. The degenerated disc exhibits unstable movement, similar to a flat tire. Approximately 20-30% of low back pain patients have been diagnosed as having spinal segmental instability. The pain may originate from stress and increased load on the facet joints and/or surrounding ligaments. In addition, pH within the disc becomes acidic from the anaerobic production of lactic acid, which irritates adjacent nerves and tissues.
Inflammation or infection within the intervertebral disc is extremely difficult to treat due to inaccessibility of drugs. Persistent pain emitting from the avascular disc is common. Intensity of the pain often is excruciating and disabling with limited options.
The method of endplate puncturing for drawing nutrients from the vertebral body to regenerate the degenerated disc is described in PCT/US2002/04301 (US national application Ser. No. 10/470,181) filed on Feb. 13, 2002 by J. Yeung and T. Yeung.
Shunts or conduits for re-establishing the exchange of nutrients and waste between the degenerative disc and body circulation is described in PCT/US2004/014368 (US national application Ser. No. 10/555,895) filed on May 7, 2004, by J. Yeung and T. Yeung.
By re-supplying the disc cells with nutrients and oxygen through disc shunt or conduit, biosynthesis of sulfated glycosaminoglycans may increase to retain additional water and sustain compressive loading. In the presence of additional oxygen, production of lactic acid may decrease, minimizing acidic irritation, increasing production of ATP, and driving biosynthesis of the water-retaining proteoglycans. Hence, segmental instability and excessive loading of facet joints will be minimized to alleviate back pain.
Hypoxia is a potent stimulus for chronic inflammation by inducing macrophages and inflammatory cytokines. The intervertebral discs are the largest hypoxic tissue in the body. In painful discs, various inflammatory cytokines, including nitric oxide, interleukins, matrix metalloproteinases, prostaglandin E2 and tumor necrosis factor alpha are found. In fact, changes in nitric oxide levels in cerebrospinal fluid from pre- to post-surgery can be a quantitative predictor of surgical outcome in pain relief.
Location of pain source is hard to fully identify and frequently puzzling. Even in the presence of sciatica, MRI often fails to show compression of neural structures. The pain may be caused by leakage of inflammatory cytokines or lactic acid from the hypoxic disc to adjacent nerve spreading the pain sensation over several spine levels.
Discs L4-5 and L5-S1 are shielded by the ilium, inaccessible by straight needle from outside to deliver the conduit into the disc. However, through the pedicle of the vertebral body, the elastically curved needle proposed in PCT/US2005/022749 (US national 11/630,706), filed on Jun. 22, 2005 by J. Yeung, can puncture through the calcified endplate to deliver the shunt or conduit for exchange of nutrients and lactate between the avascular disc and body circulation.
Coating of immuno inhibitors was also proposed in PCT/US2007/03194 (US national Ser. No. 12/223,370) filed on Feb. 5, 2007 by J. Yeung and T. Yeung on the U-shaped disc shunt. Immuno inhibitor can be coated or incorporated into the shunts to minimize fibrous formation or tissue response.